Previous trauma exposure and PTSD symptoms as predictors of subjective and biological response to stress.

OBJECTIVE: The immediate and long-term effects of traumatic exposure and subsequent posttraumatic stress reactions in people in high-risk occupations are well-documented. What is less evident is the impact of this traumatic exposure and subsequent traumatic stress symptoms on workers' response to acute stress situations. This study aimed to examine the association between prior traumatic exposure related to policing, current posttraumatic stress symptoms and biological markers of stress, and subjective appraisal of stress before, during, and after exposure to acutely stressful stimuli. METHOD: A stressful policing situation was created through the use of a video simulator room. Participants' responses to the simulated emergency were evaluated by monitoring heart rate, collecting salivatory samples for cortisol analysis, and repeated administration of a subjective measure of anxiety. RESULTS: Biological indicators of stress, as measured by cortisol level and heart rate, were not associated with previous trauma exposure or trauma symptoms; however, biological response was associated with subjective anxiety. Vulnerability to psychological stress responses during an acute stress situation was also associated with lower levels of social support, previous traumatic exposures, and preexisting symptoms of traumatic stress. The importance of these factors became more pronounced as time progressed after the event. CONCLUSION: Previous trauma exposure did not put individuals at increased risk of biological distress during an acute stress situation. However, previous trauma and reduced social supports were associated with continuing psychological distress, confirming previous research and raising concerns about the cumulative negative effects of traumatic exposure on psychological health in emergency responders.

Does posttraumatic stress disorder (PTSD) affect performance?

Research has increasingly identified alarming levels of traumatic stress symptoms in individuals working in emergency services and other high stress jobs. This study examined the effects of prior critical incident exposure and current posttraumatic symptoms on the performance of a nonpatient population, police recruits, during an acutely stressful event. A stressful policing situation was created through the use of a video simulator room that was responsive to actions of participants. The performance of participants to the simulated emergency was evaluated by 3 independent blinded raters. Prior exposure to critical incidents was measured using the Critical Incident History Questionnaire and current level of traumatic stress symptoms was measured using the Impact of Events Scale-Revised. Neither previous exposure to critical incidents nor trauma symptoms correlated with performance level. Recruits with high or severe levels of trauma symptoms did not demonstrate impairments in judgment, communication, or situation control compared with their colleagues with lesser or no trauma symptoms. On the basis of these findings, there is no reason to believe that police recruits with PTSD are prone to making errors of communication or judgment that would place them or others at increased risk.

A randomized comparison of psychological (cognitive behavior therapy), medical (fluoxetine) and combined treatment for women with premenstrual dysphoric disorder.

This study examines the relative effectiveness of cognitive behavior therapy (CBT) (ten sessions), fluoxetine (20 mg daily) and combined therapy (CBT plus fluoxetine) in women with premenstrual dysphoric disorder (PMDD). This was a randomized pragmatic treatment trial with three treatment cells. Treatment lasted for 6 months; a naturalistic follow-up was undertaken 1 year post-treatment. One hundred and eight women, satisfying the DSM-IV criteria for PMDD with 2 months' prospective confirmation were recruited into the study; sixty of these had completed 6 months of treatment and all measures before and after treatment. The main outcome measures were premenstrual scores on the Calendar of Premenstrual Experiences (COPE) and percentage of PMDD cases (DSM-IV diagnostic criteria). Significant improvement occurred in all three treatment-groups after 6 months' treatment, assessed by the COPE. Fluoxetine was associated with a more rapid improvement. There were no group differences in the percentage of DSM cases of PMDD post treatment, but at follow-up CBT was associated with better maintenance of treatment effects compared with fluoxetine. In conclusion, CBT and fluoxetine are equally effective treatments for PMDD, but the treatments have some differential effects that can be considered in treatment decisions. There appears to be no additional benefit of combining the treatments.

Personality Perceptions of Medical School Applicants.

Purpose To examine the extent to which medical school interviewers consider perceptions of applicant personality traits during a semi-structured panel interview, the interrater reliability of assessments, and the impact of such perceptions on individual admission decisions. Method Semi-structured panel interviews were conducted with applicants to the Doctor of Medicine Program at the University of Western Ontario in London, Canada. Interviewers also provided voluntary, "research only" ratings of applicants on nine relevant personality traits. Data from 345 applicants under consideration for admission were available for analysis. Results Significant correlations were observed between personality ratings and important operational variables (e.g., interview scores). Applicants who were most likely to be admitted to the program were perceived as high on certain traits (i.e., Achievement, Nurturance, Endurance, Cognitive Structure, & Order) and low on other traits (i.e., Abasement, Aggression, & Impulsivity). Statistically removing variance shared with personality ratings from interview scores resulted in different admission decisions for over 40% of the applicants. Interrater reliabilities for personality perceptions were relatively low. However, interrater reliability of the panel interview used to make admission decisions was acceptable. Nonlinear relations between personality perceptions and interview scores were also explored. Conclusion Some evidence was found that interviewers? perceptions of applicant personality may affect their judgments when assigning interview ratings. Given that non-cognitive characteristics are perceived as important in the admissions process and that perceptions of personality traits have implications for decisions about which candidates to admit, suggestions for identifying desirable non-cognitive characteristics and for increasing the quality of assessments are offered.

Can performance-feedback accuracy be improved? Effects of rater priming and rating-scale format on rating accuracy.

Performance appraisal information is often used for employee feedback and development. Research has found that assessments that are global (i.e., based on broad aspects of performance) and comparative (i.e., explicit interratee comparisons) may be most accurate in terms of Cronbach's (1955) differential accuracy, a type of accuracy that is directly relevant to the provision of feedback. Unfortunately, a global-comparative assessment may not give recipients the most useful diagnostic feedback. In this experiment, an innovative rater-priming manipulation was developed and tested on a sample of 109 participants. The priming manipulation had the effect of improving differential accuracy and providing diagnostic feedback. A 2nd independent variable involving 2 different Behavioral Observation Scale formats also was investigated. Explanations of findings, limitations of this experiment, directions for future research, and implications for performance appraisal practice are discussed.

3-(Piperazinylpropyl)indoles: selective, orally bioavailable h5-HT1D receptor agonists as potential antimigraine agents.

Clinically effective antimigraine drugs such as Sumatriptan have similar affinity at h5-HT1D and h5-HT1B receptors. In the search for a h5-HT1D-selective agonist as an antimigraine agent, a novel series of 3-(propylpiperazinyl)indoles have been synthesized and evaluated at h5-HT1D and h5-HT1B receptors. This class of compounds has provided subnanomolar, fully efficacious h5-HT1D agonists with up to 200-fold selectivity for the h5-HT1D receptor over the h5-HT1B receptor. Unlike other h5-HT1D-selective series, several propylpiperazines demonstrate good oral bioavailability. The optimum compound was 1-(3-[5-(1,2, 4-triazol-4-yl)-1H-indol-3-yl]propyl)-4-(2-(3-fluorophenyl)ethyl)p ipe razine (7f) which has excellent selectivity for h5-HT1D receptors over other 5-HT receptor subtypes and good oral bioavailability in three species. Compound 7f has been selected for further investigation as a potential development candidate in the treatment of migraine.

Synthesis and serotonergic activity of 3-[2-(pyrrolidin-1-yl)ethyl]indoles: potent agonists for the h5-HT1D receptor with high selectivity over the h5-HT1B receptor.

The design, synthesis, and biological evaluation of a novel series of 3-[2-(pyrrolidin-1-yl)ethyl]indoles with excellent selectivity for h5-HT1D (formerly 5-HT1Dalpha) receptors over h5-HT1B (formerly 5-HT1Dbeta) receptors are described. Clinically effective antimigraine drugs such as Sumatriptan show little selectivity between h5-HT1D and h5-HT1B receptors. The differential expression of h5-HT1D and h5-HT1B receptors in neural and vascular tissue prompted an investigation of whether a compound selective for the h5-HT1D subtype would have the same clinical efficacy but with reduced side effects. The pyrrolidine 3b was initially identified as having 9-fold selectivity for h5-HT1D over h5-HT1B receptors. Substitution of the pyrrolidine ring of 3b with methylbenzylamine groups gave compounds with nanomolar affinity for the h5-HT1D receptor and 100-fold selectivity with respect to h5-HT1B receptors. Modification of the indole 5-substituent led to the oxazolidinones 24a,b with up to 163-fold selectivity for the h5-HT1D subtype and improved selectivity over other serotonin receptors. The compounds were shown to be full agonists by measurement of agonist-induced [35S]GTPgammaS binding in CHO cells expressed with h5-HT receptors. This study suggests that the h5-HT1D and h5-HT1B receptors can be differentiated by appropriate substitution of the ligand in the region which binds to the aspartate residue and reveals a large binding pocket in the h5-HT1D receptor domain which is absent for the h5-HT1B receptor. The compounds described herein will be important tools to delineate the role of h5-HT1D receptors in migraine.

Synthesis and serotonergic activity of N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine and analogues: potent agonists for 5-HT1D receptors.

The synthesis and the 5-HT receptor activity of a novel series of N,N-dimethyltryptamines substituted in the 5-position with an imidazole, triazole, or tetrazole ring are described. The objective of this work was to identify potent and selective 5-HT1D receptor agonists with high oral bioavailability and low central nervous system penetration. Compounds have been prepared in which the azole ring is attached through either nitrogen or carbon to the indole. Conjugated and methylene-bridged derivatives have been studied (n = 0 or 1). Substitution of the azole ring has been explored either alpha or beta to the point of attachment to indole. In a series of N-linked azoles (X = N), simple unsubstituted compounds have high affinity and selectivity for 5-HT1D receptors. It is proposed that for good affinity and selectivity a hydrogen bond acceptor interaction with the 5-HT1D receptor, through a beta-nitrogen in the azole ring, is required. In a series of C-linked triazoles and tetrazoles (X = C), optimal affinity and selectivity for the 5-HT1D receptor was observed when the azole ring is substituted at the 1-position with a methyl or ethyl group. This study has led to the discovery of the 1,2,4-triazole 10a (MK-462) as a potent and selective 5-HT1D receptor agonist which has high oral bioavailability and rapid oral absorption. The in vitro activity and the preliminary pharmacokinetics of compounds in this series are presented.

The effect of LHRH agonist therapy in the treatment of endometriosis (English experience).

The preliminary findings of a comparative study of buserelin and danazol in the treatment of endometriosis are presented. Eighty patients with laparoscopically proven symptomatic endometriosis have been allocated at random to open treatment with intra-nasal buserelin or oral danazol. Forty-five patients have been assessed after completion of seven months treatment. Changes in endometriotic lesions have been examined by second laparoscopy and scored according to a modification of the criteria of the American Fertility Society (AFS). Both treatments were associated with reductions in modified AFS scores reflecting partial resolution of the condition. Adverse effects were reported with the use of both drugs, but appeared to be more extensive during therapy with danazol. Further evaluation and post treatment follow up are required.

Vasopressin and oxytocin responses to acute and chronic osmotic stimuli in man.

The regulation of both arginine vasopressin (AVP) and oxytocin secretion was studied during rapid and prolonged osmotic stimuli in normal adult volunteers. In five subjects given an intravenous infusion of 0.85 mol NaCl at 0.05 ml/kg per min over 2 h there was a significant (P less than 0.05) rise only in plasma AVP, with no significant change in plasma levels of oxytocin. In six further subjects 5 days of restriction to 500 ml fluid daily resulted in significant increases of both plasma and 24-h urinary AVP, whereas there was no change in corresponding oxytocin levels. During another 5-day period in which the same subjects were given an additional 200 mmol sodium as well as having their fluid intake restricted to 1000 ml daily, there were again significant rises in plasma and 24 h urinary AVP with no change in corresponding oxytocin levels. We conclude that, in man, AVP is selectively secreted in response to both dehydration and high sodium intake, whilst even after the stimulus of rapidly increasing plasma osmolality during intravenous infusion of hypertonic saline the rise in oxytocin is not statistically significant. It therefore appears unlikely that oxytocin has a significant role in the physiological control of fluid balance in man.